Ultrasound is a modem medical imaging modality using sound energy to noninvasively visualize the interior structures and organs of a patient. Pulses of high frequency sound, generally in the megaHertz (MHz) range, emitted from a hand-held transducer are propagated into the body where they encounter different surfaces and interfaces. A portion of the incident sound energy is reflected back to the transducer that converts the sound waves into electronic signals which are then presented as a two-dimensional echographic image on a display monitor.
One of the advances in ultrasound imaging has been the development of ultrasonic contrast agents. Use of contrast agents enables the sonographer to visualize the vascular system which is otherwise relatively difficult to image. In cardiology for example, ultrasound contrast injected into the bloodstream permits the cardiologist to better visualize heart wall motion with the opacification of the heart chambers. Perhaps more importantly, contrast can be used to assess perfusion of blood into the myocardium to determine the location and extent of damage caused by an infarct. Similarly, visualization of blood flow using ultrasound contrast in other organs such as the liver and kidneys has found utility in diagnosing disease states in these organs.
The first encapsulated contrast agent was developed by Tickner et al (Final Report NHLB1 Contract No. HR-62917-1A, National Institute of Health, 1977; U.S. Pat. No. 4,276,885), made of a gelatin membrane encapsulating a nitrogen bubble. The bubble diameter, while precise, was not small enough to circulate through the capillary beds and therefore was not appropriate for systemic delivery. An agent was later developed to include a lipophilic material in a saccharide composition to provide a microbubble of sufficient stability to enable pulmonary capillary transmission (Circulation 62 (Supp. III): III-34, 1980).